Felicity Thomas is Associate Editorial Director of Pharmaceutical Technology, Pharmaceutical Technology Europe, BioPharm International.

Felicity Thomas

Pharm Tech Group chats with Dr. Monika Paulė, CEO and co-founder of Caszyme about the evolution of CRISPR.

Seeking Excellence with CRISPR (BIO 2024)

Clustered regularly interspaced short palindromic repeats (CRISPR) is a novel gene-editing approach that has seen rapid commercial success with the approval of exagamglogene autotemcel (Casgevy) occurring within a span of only 11 years after its invention (1). For Dr. Monika Paulė, the advent of CRISPR came at a time when the industry and academia were “ready for something new and groundbreaking.”

Paulė is the CEO and co-founder of Caszyme—a CRISPR gene-editing platform company based in Lithuania. “We develop novel CRISPR tools, and work with other companies in their gene editing, portfolio development from discovery, research, development, and everything that's related to proteins engineering and making the CRISPR-Cas9 proteins, the best tools for the applications the companies are looking for,” she says.

However, CRISPR is not without its challenges, Paulė remarks. More tools are required to allow the technique to be more widely applicable, she explains. “We really need to find the right tool, the right technique for the right application [which] is still a little bit challenging,” Paulė adds.

“To improve the safety and efficacy of CRISPR, first of all, we have to seek excellence in CRISPR field at each and every step of CRISPR technology development and application,” summarizes Paulė. “So, we have to start from the very beginning, from very early research, and really find and develop the best tools, which are safe, which are specific enough, and which are effective enough.”

Watch the video for the full interview. Caszyme will be attending the 2024 BIO International Convention in San Diego, Calif., from June 3–6.

1. Sheridan, C. The World’s First CRISPR Therapy is Approved: Who Will Receive It? 

Dr. Monika Paulė, CEO and co-founder of Caszyme

 is an accomplished leader with over 20 years of experience in high-tech business and has a PhD in Business Management. In 2017, Monika co-founded 

, a biotechnology company that leverages CRISPR technology to empower a world that’s healthier, equitable, and more sustainable, where she acts as chief executive officer and board member.

With Monika's leadership, Caszyme has gained recognition as a renowned expert in CRISPR gene editing field among partners worldwide. By leveraging deep expertise in discovery and development of CRISPR solutions, alongside the company’s dynamic platform and strategic adaptation of complementary technologies, Caszyme is unlocking new possibilities for companies across multiple industries, from healthcare to agriculture.

Additionally, Monika serves as a vice president and board member at the life sciences association “LithuaniaBIO” and is a founder of many social initiatives such as “Women in Biotech” and “Gene Editing Summit”. Monika is an engaging speaker and moderator with experience at multiple international live events, broadcasts, and podcasts.

Videos

Communication between the manufacturing plant and retail stores. | Image Credit: © Cagkan - stock.adobe.com

Global contract development and manufacturing organization (CDMO), Sterling Pharma Solutions, announced on May 30, 2024 that it has 

invested $3 million into expanding its integrated antibody-drug conjugate (ADC) development and manufacturing capabilities

 in its Germantown, Wis. facility in the United States (1).

With the funds, a dedicated good manufacturing practice (GMP) suite will be built at the Germantown site, which will include the installation of a modular isolator that has containment capabilities down to less than one nanogram per cubic meter. Additionally, both clinical and commercial production will be possible from the site as the isolator has the capacity to perform toxin linker manufacturing up to kilogram scale. It will also be possible to weigh, dispense, and dissolve reagents easily within the fully contained environment of the isolator.

Other isolator modules are being installed for flash and high-pressure chromatography processes and for in-process analysis of products. Furthermore, a lyophilization module that is suitable for 30 L batches at -85 ºC has been commissioned.

“This investment is a crucial step in Sterling’s ambition to provide a full range of services to support our clients’ ADC development projects and accelerate programs through the clinical phase, towards commercial launch,” said Chad Telgenhof, chief commercial officer of Sterling, in a press release (1). “The new suite has been specifically designed with specialized technologies to support the manufacture of toxin-linker molecules that can be efficiently transferred to our facility in Deeside, UK [United Kingdom], in parallel, for the development and final-phase GMP conjugations of ADC drugs.”

In April 2023, Sterling’s Deeside facility in the UK was 

granted a Manufacturer’s Authorization for Investigational Medicinal Products

 from the Medicines and Healthcare products Regulatory Agency (MHRA) (2). This license allows Sterling to manufacture ADCs for clinical use at Deeside.

Sterling acquired the site in April 2021 and has invested in its expansion to develop the scientific and analytical teams, install a new water for injection plant, and establish bioconjugation and ADC manufacturing capabilities.

“The ADC facility in Deeside has over 12 years’ experience in technical development services for the industry. The granting of this license marks a major milestone for Sterling, with the company now able to integrate development and clinical manufacturing services across our network to support ADC innovators in bringing new therapies to the market,” said Kevin Cook, chief executive officer at Sterling, in a press release (2). “Our decision to expand the business in 2021 to include ADCs was strategic, to broaden our chemistry services offering to include specialized bioconjugation capabilities and has led to a number of partnerships in this area with drug developers. Our plan is to continue investment at Deeside as customer demand for these services increases to grow the business further.”

The Deeside and Germantown sites work in parallel, providing services to develop and manufacture ADC drug molecules.

1. Sterling Pharma Solutions. Sterling Pharma Solutions Expands HPAPI Capabilities in Germantown, Wisconsin, Further Strengthening Integrated ADC Development and Manufacturing Services. Press Release, May 30, 2024.
2. Sterling Pharma Solutions. Sterling Granted MIA (IMP) License by MHRA for CGMP Antibody-Drug Conjugate Manufacturing at its Facility in Deeside, UK. Press Release, April 18, 2023.

Articles

Sterling is strengthening its development and manufacturing services for ADCs with a dedicated GMP suite at its Wisconsin facility.

Sterling Invests in Expansion of Integrated ADC Services

 podcast, Felicity Thomas, European/Senior Editor, chats with Alexander Natz, Secretary-General of EUCOPE, about the European Health Data Space (EHDS), which was formally adopted by the European Parliament in April 2024. The EHDS aims to improve individual’s the access to and control of their own health data and also to allow for the secondary use of health data in research, innovation, policy-making, and regulatory activities.

 is Secretary-General of the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE). As Secretary-General, Alex advises innovative pharmaceutical and biotech companies, including start-ups, in regulatory and pricing and reimbursement matters from the European Union law and German law perspective. From 2008 to 2013, he was Head of the Brussels Office of Bundesverband der Pharmazeutischen Industrie e.V. (BPI). Before, he worked as a lawyer at Sträter Law Firm in Germany with a special focus on managed entry agreements and licensing of pharmaceuticals. Alex has also worked in the field of competition law with the European Commission and in the pharmaceutical industry. As a research assistant at Duke University (USA) he has dealt with international pharmaceutical law.

 presents the Drug Solutions podcast, where the editors will chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Join us as experts share insights into your biggest questions—from the technologies, to strategies, to regulations related to the development and manufacture of drug products.

Podcasts

In this episode, Alexander Natz from EUCOPE chats about the European Health Data Space.

Drug Solutions Podcast: All About Data: Looking at the EHDS in More Detail

people in the shape of a target with an arrow, aim | Image Credit: © tai111 - Stock.Adobe.com

Compared with small-molecule therapies, which have been in use for more than a century, the field of biological therapies is reasonably nascent. Since the approval of the first recombinant protein in the 1980s, numerous biological therapies have been developed for a variety of indications (1).

“The field of biological therapies has indeed experienced a significant expansion and transformation, largely driven by advancements in molecular and cellular biology,” says Anupreet Kaur, post-doctoral associate in the Brinson Research Group, Institute for Bioscience and Biotechnology Research, National Institute for Standards and Technology, University of Maryland. “One of the key breakthroughs has been the widespread adoption of recombinant DNA technology, which has revolutionized the production of protein therapeutics.”

“[Going back to] the end of the last century, when there were mainly small-molecule drugs on the market, [patients were typically] suffering from major side effects,” notes Peter Timmerman, head of Peptide Science at Biosynth. “[These unwanted effects] paved the way for a new generation of drugs that were more specific and more biologically based.”

A major benefit of biological therapies is their ability to reach targets that have previously been thought of as ‘undruggable’ with more traditional small-molecule therapies (2). Despite being much larger than small-molecule drugs, biological therapies feature a greater affinity and selectivity to a specific target, making them more effective with less off-target toxicity, Timmerman explains.

Specificity to molecular targets is a key attribute of monoclonal antibodies (mAbs), remarks Kaur. “This specificity allows [mAbs] to distinguish between subtle differences, such as single amino acid variation and conformational changes, enabling precise targeting of disease-related molecules,” she says. “Additionally, the bivalency of each antibody molecule contributes to the higher binding strength, which enables mAbs to bind with exceptional affinities, typically ranging from picomolar to nanomolar levels.”

This high binding strength is important for differentiating between the binding partners and for enhancing the therapeutic efficacy of the mAbs, continues Kaur. “Moreover, the Fc [fragment, crystallizable] domains of mAbs play a crucial role in [biological] properties,” she adds. “This region can engage with various components of the immune system leading to functions such as antibody-dependent cellular cytotoxicity, or complete complement dependent cytotoxicity. These effector function-enhanced antibodies have the ability to eliminate the target cells and modulate the immune response, further improving therapeutic potential.”

®, Bill Whitford, Strategic Solutions leader at Arcadis, spoke to the 

progress being made by 3D printing in commercial biologics production

Having presented on the topic during one of the sessions at INTERPHEX 2024, Whitford highlighted the utility of 3D bioprinting for cell culture. “3D culture provides many unique capabilities; it’s more biomimetic,” he said in the interview. “Actually, there’s nothing natural about growing cells in monolayer on a styrene plate, so there are many 3D culture technologies that employ many different production methods that support many categories of application and individual products.”

Additionally, Whitford alluded to the potential use of 3D bioprinting for emerging therapies, such as cell and gene therapies. “The ability now—through site-directed CRISPR [clustered regularly interspaced short palindromic repeats]-type engineering—to drive the evolution of a cell towards exactly what phenotype is required is supporting the ability to … develop the bio ink … required to get the initial print job accomplished,” he said.

Bill Whitford of Arcadis Discusses 3D Printing for Biologics (INTERPHEX 2024)

“As targets for mAb therapies are identified, fewer are agonist targets and more are antagonistic targets,” remarks Scott Rudge, founder of SynerG Biopharma Group. “When an agonist target is found, the antibody can be designed to stimulate a cell or an organ to produce a certain outcome.For example, insulin is a protein agonist, because it causes cells to take up glucose and store it as glucagon.”

However, antagonists, such as check point inhibitors, actually block something from happening, Rudge emphasizes. “If every receptor in the body needs to be inhibited or down-regulated in some way, antagonists are going to require ever increasing doses, which means higher concentration, to be administered subcutaneously or some other way less invasive than intravenous administration,” he adds.

“Subcutaneous and intramuscular delivery, in particular, require highly concentrated formulations, as the maximum volume these routes of administration can accommodate is about 1 mL,” Rudge explains. “Alternatively, other means for delivering high doses of mAbs could be found that deliver more than 1 mL. Research in these two areas is very active.”

Additionally, the development of bispecific antibodies represents a significant milestone for the biopharma industry, Kaur adds. “This platform holds promise for enhancing the efficacy, increasing the half-life, and improving the stability and specificity of biologic therapies, while minimizing the side effects,” she says.

Looking beyond antibody therapeutics, Kaur highlights RNA vaccines as a promising platform that will enable the development of novel vaccines to tackle infectious and other diseases. “Ongoing research aims to further optimise RNA vaccine platforms and expand their application beyond infectious diseases,” she says.

“Also, there are short oligonucleotide therapies, which will present a versatile and promising approach for the treatment of orphan rare diseases by targeting specific genes and other regulatory elements,” Kaur specifies. “Continued research and development efforts are focused on improving the delivery strategies, enhancing the specificity and efficacy, and expanding the clinical application of oligonucleotide-based therapeutics.”

Focusing on potential future trends for the biologics field, Hans de Backer, head of the Peptide Division, Biosynth, emphasizes that there are several key trends that will be ongoing for a long period of time. Some are more industry generalized trends, such as accelerating time-to-market and moving towards more green solutions in manufacturing; however, a more specific trend for biologics will be the drive for increasingly patient-specific solutions instead of generic ‘one-size-fits-all’ type therapies.

A further trend that is shaping the biologics sector is the development of combination therapies, whereby companies are developing these products as combination options from the outset rather than considering a potential combination later on, De Backer specifies. “The expanded range of biological and small-molecule drugs already approved can be being used during development to act on multiple pathways or the same pathways through differing mechanisms. It is therefore increasingly important for researchers to be able to access reagents (as biosimilars or generics) early in development to understand modes and mechanism of action, and routes for improving efficacy,” he says.

“All of the aforementioned trends will be mainly boosted by the introduction of artificial intelligence (AI), which is being seen in all areas playing a key role” De Backer says. In particular, he points out that AI is helping to accelerate time-to-market for drug development, all the way from discovery to production. AI is helping companies to deliver results that in turn are fitting in with funding cycles and ultimately helping them commercialize their drug products.

In terms of personalized medicine, AI will enable further personalized drug manufacture options—but also personalized prescription. AI can be used by clinicians to assess the sort of response they can expect from a therapy, which is allowing them to choose the best therapeutic option for their patients (3). “AI will definitely bring new opportunities and allow for better forecasts [of therapy outcomes], driving personalized medicine to the next level,” De Backer asserts.

Additionally, Timmerman states that he has high expectations of AI as it has the potential to provide information that hasn’t been seen before, particularly for drug discovery. Currently, when trying to look at the drug space, industry is limited to only a fraction of what is available, he emphasizes, whereas AI has the potential to be used to map out the complete drug space, enabling the identification of a greater number of novel chemical entities (4).

There are other areas where AI can provide new information, Timmerman notes. “For example, there is a new modeling program called AlphaFold that basically can predict the structure of all proteins from their primary amino acid sequences,” he says. “[So, now it is not necessary to have] any crystal structure or any other type of 3D structure to know how the protein looks and how to develop a drug against it.”

Recent research has also demonstrated the ability for AI and machine learning to speed up protein engineering (5,6). “Advancements in protein engineering have facilitated the development of novel molecular scaffolds, optimized molecular functions, and improved drug properties,” Kaur adds. “These molecule-level innovations have opened up new possibilities for creating biologics with enhanced therapeutic effects.”

“Gaining an in depth understanding of accepted and multiple antibody interactions will undoubtedly revolutionize the future of biological formulation, as this knowledge can lead to the design of excipients that have beneficial impacts on the protein structure, thereby improving quality and efficacy [of antibody therapeutics] in the future,” summarizes Kaur. “Moreover, understanding the dynamics of antibody and antigen binding properties at the molecule level will help in designing the effective next-level antibodies. Manipulating these binding properties can optimize antibody performance and specificity and affinity for specific application.”

1. Andrews, L; Ralston, S; Blomme, E.; Barnhart, K. A Snapshot of Biologic Drug Development: Challenges and Opportunities. 

, 34 (12), 1279–1285.
2. Leach, M.W.; Rottman, J.B.; Hock, B.; et al. Immunogenicity/Hypersensitivity of Biologics. 

, 42 (1), 293–300.
3. Johnson, K.B.; Wei, W.-Q.; Weeraratne, D.; et al. Precision Medicin, AI, and the Future of Personalized Health Care. 

, 14 (1), 86–93.
4. Duncan, K.K.; Rudnicki, D.D.; Austin, C.P.; Tagle, D.A. Exploring Novel Biologically-Relevant Chemical Space Through Artificial Intelligence: The NCATS ASPIRE Program. 

, 6, 1–6. DOI: 10.3389/frobt.2019.00143
5. Wait, S.J.; Expòsit, M.; Lin, S. Machine Learning-Guided Engineering of Genetically Encoded Fluorescent Calcium Indicators. 

, 4, 224–236.
6. Case, M.; Smith, M.; Vinh, J.; Thurber, G. Machine Learning to Predict Continuous Protein Properties from Binary Cell Sorting Data and Map Unseen Sequence Space. 

Felicity Thomas is the European/senior editor for Pharmaceutical Technology Group.

When referring to this article, please cite it as Thomas, F. Biologics on Target for the Future. 

A greater understanding of molecular and cellular biology and technological advancements are revolutionizing the field of biologics. 

Biologics on Target for the Future

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On 6 May 2024, the King’s Awards for Enterprise 2024 winners were announced and included pharmaceutical company, Nanomerics, and several companies that provide services to the pharmaceutical industry. The awards (previously known as the Queen’s Awards for Enterprise) recognize outstanding achievements in enterprise across four categories: innovation; international trade; sustainable development; and promoting opportunity (through social mobility) (1).

Nanomerics, a spin-out from University College London, received the King’s Award for Enterprise in the category of Innovation. The company has been recognized for its active excipient platform for precision medicines, Molecular Envelope Technology (MET). MET works by encapsulating nano-scaled drug doses and allowing water-insoluble compounds to pass through mucosal barriers, which increases efficacy of the drug product and reduces side effects (2).

“It is a real honour to win the King’s Award for Enterprise 2024 in the Innovation category,” said Professor Andreas G. Schätzlein, CEO of Nanomerics, in a press release (2). “This award recognizes the efforts we are making to ensure that drug development has a higher likelihood of success.”

However, the majority of the winners from the pharma industry for 2024 have been recognized for their achievements in international trade. Gentronix, for example, which is a contract research organization that specializes in toxicology, received the award as a result of achieving triple-figure revenue growth thanks to its international expansion (3); and, Seda Pharmaceutical Development Services, which works with biotech companies to help design, develop, and market novel medicinal products, was recognized for its “outstanding short-term growth in overseas sales” (4).

Furthermore, several consulting groups were also recognized in this year’s awards for their successes in international trade. Among these groups were Uptake Strategies, which is a global healthcare consultancy for the pharma and biotech industry (5); and DLRC, which is global consultancy providing regulatory services to pharma and medtech companies of all sizes (6).

The full list of winners for 2024 can be found in a 

1. The London Gazette. The King’s Awards for Enterprise. 

 (accessed 13 May 2024).
2. Nanomerics. Nanomerics Wins the United Kingdom King’s Award for Enterprise 2024. Press Release, 6 May 2024.
3. Tate, M. Genotronix Recognized with King’s Award After Record International Growth. Press Release, 7 May 2024.
4. Seda Pharmaceutical Development Services. Stockport Based, Seda Pharmaceutical Development Services Wins King’s Award for Enterprise 2024. Press Release, 6 May 2024.
5. King, C. Uptake Honoured in the King’s Awards for Enterprise 2024. Press Release, 6 May 2024.
6. DLRC. DLRC Achieves King’s Award for Enterprise in International Trade. Press Release, 6 May 2024.
7. The London Gazette. The King’s Awards for Enterprise. 

When referring to this article, please cite it as Thomas, F. Streamlining Variations. 

Pharmaceutical company, Nanomerics, and several companies that work with the pharmaceutical industry have been recognized by King Charles III for business achievements.

Royal Recognition

Text sign showing Industry News. Business photo text delivering news to the general public or a target public | Image Credit: © Artur - stock.adobe.com

Novartis announced, in an April 23, 2024 press release, that its radioligand therapy, Lutathera, has gained FDA approval as a treatment for pediatric patients aged 12 years and older with somatostatin receptor-positive (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs), inclusive of foregut, midgut, and hindgut GEP-NETs.

“Lutathera is now the very first therapy approved specifically for children with GEP-NETs, offering new hope to young patients living with this rare cancer,” said Tina Deignan, Therapeutic Area head, Oncology US, Novartis, in the press release (1). “Radioligand therapies have extraordinary potential to shape the future of cancer care. With this approval, we have taken another vital step toward fulfilling that vision, strengthening our commitment to researching and developing the RLT [radioligand therapy] platform across multiple cancer types and treatment settings.”

FDA’s approval was based on the ongoing open-label, multicenter, single-arm, Phase II NETTER-P trial, which has been designed to evaluate the safety and dosimetry of Lutathera in patients between the ages of 12 and 18 years old who have SSTR+ GEP-NETs (2). The results of the Phase II NETTER-P trial were consistent with those found in adult patients via the NETTER-1 trial.

“While GEP-NETs in children and adolescents are rare, the impact can be devastating. [This] approval addresses a critical need for new treatment options for these vulnerable patients,” said Dr. Theodore Laetsch, trial investigator and director, Developmental Therapeutics Program, Children’s Hospital of Philadelphia (CHOP), a NETTER-P clinical trial site, in the press release (1). “The introduction of radioligand therapy significantly advanced how we treat GEP-NETs, and I’m encouraged that younger patients now have the potential to benefit from this innovation.”

Additionally, in January 2024, Novartis announced the results of the Phase III NETTER-2 trial, demonstrating that Lutathera plus long-acting release (LAR)octreotide reduced the risk of disease progression or death by 72% when used as a first-line therapy in adult patients with SSTR+ well-differentiated grade 2/3 advanced GEP-NETs (3).

“This is the first positive Phase III trial of a radioligand therapy in the first-line setting, and the overall efficacy and safety results are amongst the most clinically relevant observed to date in this kind of advanced cancer, addressing a significant unmet need for patients with newly diagnosed advanced GEP-NETs,” said Jeff Legos, global head of Oncology Development at Novartis, in a press release (3). “The positive results are a significant advancement and further reaffirm our strategy to research and develop radioligand therapies in earlier lines of treatment or stages of disease to improve outcomes for patients.”

1. Novartis. Novartis Radioligand Therapy Lutathera FDA Approved as First Medicine Specifically for Pediatric Patients with Gastroenteropancreatic Neurodocrine Tumors. Press Release, April 23, 2024.
2. NIH. Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients with GEP-NETs and PPGLs. 

 (accessed April 24, 2024).
3. Novartis. Novartis Lutathera Significantly Reduced Risk of Disease Progression or Death by 72% as First-Line Treatment for Patients with Advanced Gastroenteropancreatic Neuroendocrine Tumors. Press Release, Jan. 19, 2024.

FDA has granted approval for the use of Novartis’ radioligand therapy, Lutathera, to treat pediatric patients with gastroenteropancreatic neuroendocrine tumors.